inpefa

Important safety information

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INPEFA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. ( 5.1 ) Volume Depletion: Before initiating, correct volume status. Monitor for signs and symptoms of hypotension during therapy. ( 5.2 ) Urosepsis and Pyelonephritis: Monitor for signs and symptoms during therapy and treat promptly. ( 5.3 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Lower dose of insulin or insulin secretagogue may be required. ( 5.4 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Monitor for pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. Discontinue INPEFA and treat urgently. ( 5.5 ) Genital Mycotic Infections : Monitor and treat as appropriate. ( 5.6 ) 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, INPEFA significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose cotransporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses of INPEFA. INPEFA is not indicated for glycemic control. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using SGLT2 inhibitors. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include acute febrile illness, reduced caloric intake, ketogenic diet, surgery, insulin dose reduction, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing INPEFA [see Clinical Pharmacology ( 12.3 )]; however, there have been postmarketing reports of ketoacidosis and glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue INPEFA, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting INPEFA. Withhold INPEFA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume INPEFA when the patient is clinically stable and has resumed oral intake [see Dosage and Administration ( 2.3 )] . Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue INPEFA and seek medical attention immediately if signs and symptoms occur. 5.2 Volume Depletion INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m 2 ), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension [see Adverse Reactions ( 6.1 ) and Use in Specific Populations ( 8.5 , 8.6 )]. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function. Monitor for signs and symptoms of hypotension, and renal function after initiating therapy. 5.3 Urosepsis and Pyelonephritis Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions ( 6.1 )] . 5.4 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue [see Adverse Reactions ( 6.1 )] . Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when these agents are used in combination with INPEFA. 5.5 Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) Reports of necrotizing fasciitis of the perineum (Fournier's Gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with INPEFA presenting with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor blood glucose levels, and provide appropriate alternative therapy for heart failure. 5.6 Genital Mycotic Infections INPEFA increases the risk of genital mycotic infections. Patients with a history of genital mycotic infections were more likely to develop genital mycotic infections [see Adverse Reactions ( 6.1 )] . Monitor and treat appropriately. 5.7 Positive Urine Glucose Test Monitoring glucose levels with urine glucose tests is not recommended as SGLT2 inhibition increases urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glucose levels. 5.8 Interference with 1,5-anhydroglucitol (1,5-AG) Assay Monitoring glucose levels with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glucose levels in patients taking SGLT2 inhibitors. Use alternative methods to monitor glucose levels.